Transdermal drug delivery systems have, in recent years, become an increasingly important means of administering drugs. Such systems offer advantages clearly not achievable by other modes of administration such as avoiding introduction of the drug through the gastro-intestinal tract or punctures in the skin to name a few.
Presently, there are two types of transdermal drug delivery systems, i.e., "Passive" and "Active." Passive systems deliver drug through the skin of the user unaided, an example of which would involve the application of a topical anesthetic to provide localized relief, as disclosed in U.S. Pat. No. 3,814,095 (Lubens). Active systems on the other hand deliver drug through the skin of the user using iontophoresis, which according to Stedman's Medical Dictionary, is defined as "the introduction into the tissues, by means of an electric current, of the ions of a chosen medicament."
Conventional iontophoretic devices, such as those described in U.S. Pat. Nos. 4,820,263 (Spevak et al.), 4,927,408 (Haak et al.) and 5,084,008 (Phipps), the disclosures of which are hereby incorporated by reference, for delivering a drug or medicine transdermally through iontophoresis, basically consist of two electrodes, i.e., an anode and a cathode. Usually, electric current is driven from an external supply into the skin at the anode, and back out at the cathode. Accordingly, there has been considerable interest in iontophoresis to perform delivery of drugs for a variety of purposes.
However, several disadvantages and limitations have been associated with the use of such devices, including unacceptable levels of sensations due to current flow during iontophoresis, which in severe cases can be painful.
Attempts to reduce or mitigate such unacceptable levels of sensation have included employing materials between the electrode and the patient's skin as disclosed in U.S. Pat. No. 4,211,222 (Tapper), gradually imposing the current as disclosed in U.S. Pat. No. 4,340,047 (Tapper), pulsating the voltage as disclosed in U.S. Pat. No. 4,764,164 (Sasaki), reducing the current prior to switching polarity as disclosed in U.S. Pat. No. 4,406,658 (Lattin et al.), and alternating between biphasic stimulation and iontophoretic delivery as disclosed in U.S. Pat. No. 4,456,102 (Lattin), the disclosures of which are hereby incorporated by reference. Nevertheless, despite such attempts unacceptable sensation levels remain, especially when drug is delivered with high efficiency.
In addition to the above, amounts of a multivalent ion such as calcium, magnesium, phosphate and zinc have been included in the drug reservoir to reduce sensation as disclosed in U.S. Pat. No. 5,221,254 (Phipps), the disclosure of which is hereby incorporated by reference. However, the presence of such multivalent ions competes with the agent to be delivered and reduces the overall effect.
Specifically, unacceptable sensation levels have even been encountered during the iontophoretic delivery of local anesthetics, especially when rapid onset of the local anesthetic is desired involving, for example, the use of Novocaine, which is usually injected prior to dental work to relieve pain or the use of Lidocaine, which is usually applied as a topical, local anesthetic as disclosed in U.S. Pat. No. 4,950,229 (Sage, Jr. et al.), the disclosure of which is hereby incorporated by reference.
Thus, there has been a need for an iontophoretic drug delivery device, as well as a method for reducing skin pain, which would eliminate the problems and limitations associated with the prior devices discussed above, most significant of the problems being unacceptable levels of sensation. In addition, there has been a need for a device, which would reduce sensation without affecting the overall effect of the agent to be delivered.